OBJECTIVES: The purpose of this study was to assess the incidence, temporal characteristics, and risk factors associated with azimilide-associated torsades de pointes (TdP) ventricular tachycardia. BACKGROUND: Azimilide dihydrochloride is a class III antiarrhythmic drug possessing Ikr and Iks channel-blocking properties. METHODS: Oral azimilide (75 to 125 mg/day) was taken by 5,375 patients in 19 clinical trials conducted at 775 international centers. Of 3,964 patients in double-blind studies, 1,427 had a history of atrial fibrillation or other supraventricular arrhythmia, 510 had an implantable cardioverter-defibrillator, and 2,027 were post-myocardial infarction patients with a left ventricular ejection fraction < or =35%. RESULTS: The TdP occurred in 56 patients assigned to azimilide, was dose-related, and tended to occur earlier with an azimilide-loading regimen. Forty-three percent of TdP patients had a QT interval corrected by Bazett's formula, for heart rate, (QTc) > or =500 ms at the time of or before the TdP occurrence. Significant risk factors using logistic regression were increasing age, female gender, diuretic use, and lack of aspirin use. CONCLUSIONS: Azimilide-associated TdP has characteristics and risk factors similar to other Ikr blockers. However, there is a distinctive temporal profile. The TdP events are not concentrated in the first week. The azimilide-associated TdP rate is 1% (95% confidence interval 0.78 to 1.35) and is not increased in patients with low left ventricular ejection fraction, even in women.